We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Tertiary lymphoid structures critical for prognosis in endometrial cancer patients.
- Authors
Horeweg, Nanda; Workel, Hagma H.; Loiero, Dominik; Church, David N.; Vermij, Lisa; Léon-Castillo, Alicia; Krog, Ricki T.; de Boer, Stephanie M.; Nout, Remi A.; Powell, Melanie E.; Mileshkin, Linda R.; MacKay, Helen; Leary, Alexandra; Singh, Naveena; Jürgenliemk-Schulz, Ina M.; Smit, Vincent T. H. B. M.; Creutzberg, Carien L.; Koelzer, Viktor H.; Nijman, Hans W.; Bosse, Tjalling
- Abstract
B-cells play a key role in cancer suppression, particularly when aggregated in tertiary lymphoid structures (TLS). Here, we investigate the role of B-cells and TLS in endometrial cancer (EC). Single cell RNA-sequencing of B-cells shows presence of naïve B-cells, cycling/germinal center B-cells and antibody-secreting cells. Differential gene expression analysis shows association of TLS with L1CAM overexpression. Immunohistochemistry and co-immunofluorescence show L1CAM expression in mature TLS, independent of L1CAM expression in the tumor. Using L1CAM as a marker, 378 of the 411 molecularly classified ECs from the PORTEC-3 biobank are evaluated, TLS are found in 19%. L1CAM expressing TLS are most common in mismatch-repair deficient (29/127, 23%) and polymerase-epsilon mutant EC (24/47, 51%). Multivariable Cox regression analysis shows strong favorable prognostic impact of TLS, independent of clinicopathological and molecular factors. Our data suggests a pivotal role of TLS in outcome of EC patients, and establishes L1CAM as a simple biomarker. Tertiary lymphoid structures (TLS) are associated with a reduced risk of cancer recurrence and improved response to immune checkpoint blockade in several tumor types. Here the authors identify L1CAM as a marker for mature TLS and show that the presence of TLS is associated with favorable prognosis in patients with endometrial cancer from the PORTEC-3 trial.
- Subjects
TERTIARY structure; CANCER prognosis; BREAST cancer prognosis; B cells; GERMINAL centers; IMMUNE checkpoint proteins
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-29040-x